Between January 1981 and December 1983, a prospective therapeutic trial of detorubicin (14-diethoxyacetoxy-daunorubicin [DTR]) was conducted in 40 patients with histologically proven malignant mesothelioma (MM). DTR was given intravenously at 40 mg/m2 on days 1, 2, and 3 for five 21-day cycles, then 40 mg/m2 once every 21 days. Thirty-five patients (32 with pleural MM, 3 with peritoneal MM) were eligible. The overall median survival from onset of chemotherapy was 17 months. Complete relief from chest pain was observed in 8 of 15 cases (53%). Of 21 patients with measurable disease, there were 2 complete responses (10%) and 7 partial responses (33%). Median duration of response was 30 weeks. Congestive cardiac failure developed in two patients after 1100 and 1600 mg/m2 of DTR, respectively. Hematologic toxicity was moderate. This study demonstrates that DTR is effective against MM.